1. Field of the Invention
The present invention relates to a method for the synthesis of an organic sulfide by the reaction of a sulfide with an organic sulfur-indium complex. More specifically, the conventional synthesis method for the formation of carbon sulfur bonds is carried out by the reaction between a nucleophile and an electrophile in the presence of a transition metal catalyst. An organic halide compound is used as an electrophile and a thiol is used as a nucleophile. A thiolate ion instead of a thiol is used as a nucleophile because a thiolate ion has more nucleophilicity than a thiol. And this conventional synthesis method requires high temperature and long reaction time. Therefore, an object of this invention is to provide a new type of reagent for the increase of nucleophilicity of a thiol and a high yield of organic sulfide in a relatively short reaction time. The synthesis methods of this invention are useful for the preparation of an organic sulfide whose synthesis method is not reported so far and which is difficult to be prepared. Another object of the present invention is to provide an effective and new synthesis method which can be carried out without an excess amount of reagents. The yield is quantitative when a nucleophile containing two or more nucleophilic sites in the compound is used.
2. Description of the Related Art
The conventional carbon-sulfur bonds formation reaction between an aromatic halide and a thiol in the presence of transition metal catalyst is carried out by the use of an atmospherically unstable strong base instead of a general base. This reaction requires long reaction time and high temperature. It is reported that a transition metal catalyst such as, Cu, Co, Ni, or Pd is used for the reaction. However, an excess amount of reagents, expensive ligands and additives are required for the formation of carbon-sulfur bonds in the conventional method. Therefore, the carbon-sulfur bond formation is difficult under mild reaction conditions and also it is difficult to control the regioselectivity of the reaction depending on the functional group of the substrate when a transition metal catalyst is not used in the reaction.
The formation of carbon-sulfur bonds by the reaction of aromatic triflate with a thiol in the presence of sodium t-butoxide and a palladium catalyst is reported (N. Zheng, et al., J. Org. Chem., 63, 9606 (1998)). However, the usefulness of this method has a limit and heating is required for 24 hours.
The formation of carbon-sulfur bonds by the reaction of aromatic iodide with a thiol in the presence of potassium t-butoxide and a palladium catalyst is reported (A. Schlapbach, et al., Tetrahedron, 57, 3069 (2001)). The reaction is limited to an aromatic iodide and potassium t-butoxide is necessarily required.
The formation of carbon-sulfur bonds by the reaction of aromatic boronic acid with a thio imide in the presence of a copper catalyst is reported (L. S. Leibeskind et al., Org. Lett., 4, 4309 (2002)). 24 hours of reaction time is required.
The formation of carbon-sulfur bonds by the reaction of aromatic iodide with a thiol in the presence of sodium t-butoxide and a copper neocuprine catalyst is reported (D. Venkataraman, et al., Org. Lett., 4, 2803 (2002)). However, the usefulness of this method is limited to aromatic iodide and the reaction is carried out for 24 hours at 110 degrees Celsius.
The formation of carbon-sulfur bonds by the reaction of aromatic halide with a thiol in the presence of a palladium catalyst and various kinds of base is reported (R. Lerebours, et al., J. Org. Chem., 68, 7077 (2003)). The reaction is carried out for 48 hours in toluene at high temperature.
The formation of carbon-sulfur bonds by the reaction of unsaturated iodide with a thiol in the presence of a copper-neocuprine catalyst and K3PO4 is reported (D. Venkataraman, et al., Org. Lett., 6, 5005 (2004)). However, the usefulness of this method is limited to unsaturated iodide and the reaction is carried out at 110 degrees Celsius.
The formation of carbon-sulfur bonds by the reaction of aromatic halide with a thiol in the presence of a palladium catalyst and Cs2CO3 is reported (P. Zhang et al., J. Org. Chem., 69, 8886 (2004)). This reaction requires an excess amount of reagents and over 20 hours of heating.
The formation of carbon-sulfur bonds by the reaction of aromatic halide with a thiol in the presence of a palladium catalyst and i-Pr2NEt base is reported (T. Itoh et al., Org. Lett., 6, 4587 (2004)). This reaction requires an excess amount of catalyst and long reaction time
The formation of carbon-sulfur bonds by the reaction of aromatic halide with a thiol in the presence of palladium catalyst and sodium t-butoxide is reported (S. L. Buchwald, et al., Tetrahedron, 60, 7397 (2004)). This reaction requires a strong base and is carried out for 18 hours in dioxane.
The formation of carbon-sulfur bonds by the reaction of aromatic halide with a thiol in the presence of palladium catalyst and K2CO3 is reported (P. Belslin, et al., Tetrahedron, 61, 5253 (2005)). This reaction is carried out for 24 hours at 140 degrees Celsius in xylene.
The formation of carbon-sulfur bonds by the reaction of unsaturated halide with a thiol in the presence of a copper diammine catalyst is reported (I. Tellitu, et al., Chem. Eur. J., 13, 5100 (2006)). This reaction requires two times usage of reagents and is carried out for 10 hours at 120 degrees Celsius.
The formation of carbon-sulfur bonds by the reaction of aromatic iodide with a thiol in the presence of a copper-tripod catalyst and Cs2CO3 is reported (Y. J. Chen, et al., Org. Lett., 8, 5609 (2006)). Aromatic iodide is the only used halide and the reaction is carried out for 24 hours of heating.
The formation of carbon-sulfur bonds by the reaction of aromatic halide with a thiol in the presence of a cobalt-zinc catalyst and pyridine is reported (C. H. Cheng, et al., Org. Lett., 8, 5613 (2006). More than one equivalent of zinc is used as a reducing agent and the reaction is carried out for 10 hours of heating.
The formation of carbon-sulfur bonds by the reaction of aromatic halide with a thiol in the presence of a palladium catalyst is reported (J. F. Hartwig, et al., J. Am. Chem. Soc., 128, 2180, (2006)). The ligand is specially designed for this reaction and the reaction should be carried out under strong basic conditions at high temperature.
The formation of carbon-sulfur bonds by the reaction of aromatic halide with a thiol in the presence of a Ni—NHC catalyst and potassium t-butoxide is reported (J. Y. Ying, et al., Org. Lett., 9, 3495 (2007)). This reaction requires a strong base and 16 hours of heating.
The formation of carbon-sulfur bonds by the reaction of aromatic iodide with a thiol in the presence of a copper diammine catalyst is reported (E. Dominguez, et al., Chem. Eur. J., 13, 5100 (2007)). Aromatic iodide is the only used halide and this reaction is carried out for more than 10 hours at 120 degrees Celsius in water.